Interleukin 1β and tumour necrosis factor α Inhibit acid secretion in cultured rabbit parietal cells by multiple pathways
Interleukin 1β and tumour necrosis factor α Inhibit acid secretion in cultured rabbit parietal cells by multiple pathways
复制标题
DOI：
10.1136/gut.42.2.227
复制
发表时间：
1998-02-01
期刊：
影响因子：
24.5
通讯作者：
Calam, J
中科院分区：
文献类型：
--
作者：
Beales, ILP;Calam, J
背景-细胞因子白细胞介素1 β（IL-1 β）和肿瘤坏死因子α（TNF-α）是胃酸分泌的抑制剂，当系统给药时，目的-研究IL-1 β和TNF-α对培养的分泌酸的壁细胞的抑制作用，以确定这种抑制的机制。通过胶原酶-EDTA消化和逆流淘析制备细胞。通过氨基比林蓄积评估酸分泌活性。结果-IL-1 β和TNF-α以剂量依赖性方式抑制基础和刺激酸分泌;在10 ng/ml时均观察到接近最大效应。预处理15分钟时抑制作用最大，但预孵育18小时时可观察到抑制作用。这两种细胞因子抑制组胺，卡巴胆碱，胃泌素，毛喉素，和A23187刺激酸分泌，但没有影响刺激二丁酰-cAMP。酸分泌的抑制并不伴随着放射性配体与组胺H-2或胃泌素/CCKB受体结合的变化。百日咳毒素可阻断组胺和毛喉素刺激的抑制作用。酪氨酸激酶抑制剂除莠霉素减少了TNF-α对所有刺激的抑制作用，但只减少了IL-1 β对组胺和forskolin stimulation. Conclusions的影响-IL-1 β和TNF-α似乎抑制壁细胞酸分泌的多个途径;抑制发生在受体后水平，涉及百日咳毒素和酪氨酸激酶依赖和独立的途径。粘液分泌细胞因子可能在胃酸分泌的调节中起重要作用。
Background-The cytokines interleukin 1 beta (IL-1 beta) and tumour necrosis factor alpha (TNF-alpha) are inhibitors of gastric acid secretion when administered systematically.Aims-To investigate the inhibitory effect of IL-1 beta and TNF-alpha on cultured, acid secreting parietal cells in order to determine the mechanism of this inhibition.Methods-Rabbit parietal. cells were prepared by collagenase-EDTA digestion and counter flow elutriation. Acid secretory activity was assessed by aminopyrine accumulation,Results-IL-1 beta and TNF-alpha inhibited basal and stimulated acid secretion in a dose dependent manner; near maximal effects were seen with both at 10 ng/ml. Inhibition was maximal with 15 minutes pretreatment but seen with up to 18 hours of preincubation. Both cytokines inhibited histamine, carbachol, gastrin, forskolin, and A23187 stimulated acid secretion but had no effect on stimulation by dibutyryl-cAMP. inhibition of acid secretion was not accompanied by a change in radioligand binding to histamine H-2 or gastrin/CCKB receptors. Pertussis toxin abolished the inhibitory effects on histamine and forskolin stimulation. The tyrosine kinase inhibitor herbimycin reduced the inhibitory effects of TNF-alpha against all stimuli but only reduced the effects of IL-1 beta against histamine and forskolin stimulation.Conclusions-IL-1 beta and TNF-alpha seem to inhibit parietal cell acid secretion by multiple pathways; the inhibition occurs at postreceptor level and involves pertussis toxin and tyrosine kinase dependent and independent pathways. Mucosal production of cytokines may be important in the regulation of gastric acid secretion.